Acute otitis media (AOM) is a common inflammatory disease of the middle ear characterized by pain and hearing loss. Antibiotics treat infection and often result in symptomatic relief, but do not target inflammatory parameters such as middle ear effusion (MEE), which can cause hearing loss and other complications. No therapies directly target middle ear inflammation. Targeted Gene Delivery, Inc. has identified and characterized a peptide (peptide P13) that interferes with intracellular pro-inflammatory signaling and cell activation that results from the interaction of pathogen products with immune cells. Data generated during the Phase II study demonstrated a dramatic reduction in middle ear inflammation in a murine model using heat- inactivated S. pneumoniae and H. influenzae injected simultaneously with peptide treatment. The purpose of this Phase II Competing Renewal proposal will be to generate pre-clinical efficacy and toxicity data to support an Investigational New Drug (IND) application to use peptide P13 as an anti-inflammatory therapy in AOM. We will examine peptide P13 efficacy in a clinically relevant model using viable bacteria and delayed peptide treatment. When these studies are completed, we will begin the pre-clinical toxicity testing necessary to initiate clinical trials. These studies have the potential to define a new approach to treating middle ear inflammation and will have application for other clinical conditions in which infections lead to detrimental inflammatory disease. Acute otitis media (AOM) is often characterized by prolonged inflammation that causes hearing loss and other complications. Antibiotics treat infection, but do not target inflammation. We have identified a novel therapeutic peptide that has demonstrated significant anti-inflammatory effects in a murine model of AOM. Through efficacy and toxicity testing, this peptide will be developed as a new therapy for treatment of AOM [unreadable] [unreadable] [unreadable]